Targeting Chemokine Receptors to Modulate MDSCs for Cancer Therapy

Host anti-tumor responses, including the actions of cytotoxic T cells, play a key role in targeting tumors, but can be hindered by multiple mechanisms active within the tumor microenvironment. One such mechanism involves the recruitment and expansion of immunosuppressive cells such as myeloid derived suppressor cells (MDSCs) in the tumor microenvironment. We have utilized two transplantable lung tumor cell lines (TC1 and LLC) to address the role of certain chemokine receptors in MDSC associated tumor progression. In addition, we used a thioglycolate-induced peritonitis model of inflammation to validate the ability of chemokine receptor antagonists to inhibit trafficking of MDSCs to the site of inflammation. Finally, we tested the compounds for their ability to impair chemokine signaling within established tumors and promote antitumor immunity. In summary, genetic and pharmacologic data indicate that targeting chemokine receptors to modulate MDSCs may be an important new component of immuno-oncology based therapies.